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dc.contributor.authorMiddleton, M. R.
dc.contributor.authorDean, Emma J
dc.contributor.authorEvans, T. R. J.
dc.contributor.authorShapiro, G. I.
dc.contributor.authorPollard, J.
dc.contributor.authorHendriks, B. S.
dc.contributor.authorFalk, M.
dc.contributor.authorDiaz-Padilla, I
dc.contributor.authorPlummer, R.
dc.date.accessioned2021-07-19T10:28:48Z
dc.date.available2021-07-19T10:28:48Z
dc.date.issued2021en
dc.identifier.citationMiddleton MR, Dean E, Evans TRJ, Shapiro GI, Pollard J, Hendriks BS, et al. Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours. Br J Cancer. 2021 May 26.en
dc.identifier.pmid34040175en
dc.identifier.doi10.1038/s41416-021-01405-xen
dc.identifier.urihttp://hdl.handle.net/10541/624100
dc.description.abstractBackground: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). We assessed multiple ascending doses of berzosertib + gemcitabine ± cisplatin in patients with resistant/refractory advanced solid tumours. Methods: We evaluated the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of intravenous berzosertib + gemcitabine ± cisplatin using a standard 3 + 3 dose-escalation design. The starting doses were berzosertib 18 mg/m2, gemcitabine 875 mg/m2 and cisplatin 60 mg/m2. Results: Fifty-two patients received berzosertib + gemcitabine and eight received berzosertib + gemcitabine + cisplatin. Four patients receiving berzosertib + gemcitabine had a total of seven dose-limiting toxicities (DLTs) and three receiving berzosertib + gemcitabine + cisplatin had a total of three DLTs. Berzosertib 210 mg/m2 (days 2 and 9) + gemcitabine 1000 mg/m2 (days 1 and 8) Q3W was established as the recommended Phase 2 dose (RP2D); no RP2D was determined for berzosertib + gemcitabine + cisplatin. Neither gemcitabine nor cisplatin affected berzosertib PK. Most patients in both arms achieved a best response of either partial response or stable disease. Conclusions: Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s41416-021-01405-xen
dc.titlePhase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumoursen
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, University of Oxford, Oxford, UK.en
dc.identifier.journalBritish Journal of Canceren
dc.description.noteen]
refterms.dateFOA2021-07-26T11:59:31Z


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